PKA - Conserved Residues 43-297 Catalytic Core

Residue
Location
Feature
49LYSIForm hydrophobic pocket for adenine
50GLY

51X

52GLY

53X

54X

55GLY

56X

57VAL

I Beta 1 and Beta 2Nucleotide binding motif i.e.

"glycine rich loop"

Amides of 53SER, 54PHE, 55GLY hydrogen bond to ATP beta phosphate


Hydrophobic pocket for adenine

72LYSIIHydrogen bond to alpha phosphate and beta phosphate of ATP

Hydrogen bond to 91GLU

Hydrogen bond to 184ASP

91GLUIIISee 72LYS
121GLU

123VAL

127GLU

V (Linker) Hydrogen bond to adenosine

also bond to ARG-ARG-X-SER substrate recognition site

120MET

122TYR

123VAL

V Hydrophobic pocket for adenosine
164HIS

165LYS

166ASP

167LEU

168LYS

169X

170GLU

171ASN

VIB "catalytic loop"

Accepts proton from substrate hydroxyl

Neutralizes charge on gamma P

Hydrogen bonds to ribose ring and forms ion pair with second ARG of substrate

Chelation with Mg++

184ASP

185PHE

186GLU

VII Conserved triplet Orients gamma P and chelates Mg++
197THRVIIIPhosphorylation site
198LEU

199CYS

202PRO

205LEU

VIIIForms hydrophobic pocket for substrate binding
206ALA

207PRO

208GLU

VIII

Ion pair with 280ARG stabilizes large lobe
220ASPIXStabilizes catalytic loop via hydrogen bonds to 164TYR and 165LYS
230GLUIXSubstrate recognition
235TYR

236PRO

237ASP

238PHE

239PHE

IXHydrophobic pocket for substrate
280ARG
HIS-X-aromatic-hydrophobic Chemical boundary